Did implementation of three ligament tenodesis improve patient outcome after chronic scapholunate instability? A retrospective study.

INTRODUCTION: Scapholunate instability frequently leads to chronic pain or even severe osteoarthritis of the wrist. Most favored reconstruction techniques of chronic SL-ligament injuries are based on the usage of a tendon, although there is still a lack of consensus which technique is superior. MATERIALS AND METHODS: In a retrospective cohort analysis we compared 9 patients who underwent SL-ligament repair according to Van den Abbeele and 12 patients who underwent modified three ligament tenodesis according to Garcia-Elias, performed at a single institution. RESULTS: Follow-up of Van den Abbeele group was 36-120 months and 13-39 months in the Garcia Elias cohort. Although both techniques showed good functional outcome in most cases, modified three ligament tenodesis seemed to be advantageous regarding wrist range of motion (162°) compared to Van den Abbeele cohort (87°). Moreover, pain score showed significant differences between the two cohorts during follow up (VAS Van den Abbeele 4.2; VAS Garcia Elias 1.7). Interestingly, DASH-score (16.1 Van den Abbeele; 16.8 Garcia Elias) and modified mayo wrist score (72 Van den Abbeele; 69 Garcia-Elias) did not show any differences between the two patient cohorts. CONCLUSIONS: Via implementation of modified three ligament tenodesis as a standard of care for our patients we could improve the functional outcome after SL-ligament injuries and effectively decrease postoperative pain.

Epididymitis: ascending infection restricted by segmental boundaries.

STUDY QUESTION: Is the regionalization of epididymitis related to epididymal segmentation? SUMMARY ANSWER: We show for the first time that luminal ascent of bacteria is strictly gated by epididymal segment boundaries, involving ductal constriction adjacent to the infected area. WHAT IS KNOWN ALREADY: The epididymal duct is a continuous, unbranched tube, coiled into segments that are divided by connective tissue septa. Sonographic analysis indicates that swelling associated with epididymitis is predominant in the cauda region. Epididymal segmentation has never been investigated in the context of pathological alterations. STUDY DESIGN, SIZE, AND DURATION: We analyzed segment-specific changes in the epididymal duct in a mouse model and in men. In the mouse epididymitis model (3 days post-infection, injection of bacteria into the lumen of the vas deferens), two Escherichia coli strains were tested: a uropathogenic strain CFT073 (UPEC, n = 7) and a fecal non-pathogenic strain NPEC470 (NPEC, n = 5). Two control groups: phosphate-buffered saline, sham-treated animals (n = 4) and untreated mice (n = 8). In addition, segmentation was verified by ex vivo injection of dye into the interstitial spaces of untreated mouse epididymides. Histological findings were compared with specimens from epididymitis patients (n = 10, age range 14-78, median 60 years) who underwent surgical intervention; control: samples from patients without epididymitis (n = 16, age range 38-87, median 73 years). PARTICIPANTS/MATERIALS, SETTING, AND METHODS: We investigated the ascending infections by detailed histological analysis in correlation with local infection status in a mouse epididymitis model. As a proof of concept, rare patient material from two archives was analyzed: epididymides from patients who underwent surgical intervention for persisting epididymitis, and for control, histologically normal epididymides from men who underwent orchiectomy for therapy of prostatic carcinoma. MAIN RESULTS AND THE ROLE OF CHANCE: Luminal ascent of E. coli in mice was strictly gated by epididymal segment boundaries. In the mouse model, both strains of E. coli were detected exclusively in the distal cauda segment associated with damage of the epithelium and muscle layer. Ductal constriction occurred in the non-infected upstream segments of infected area, putatively blocking further luminal ascent of bacteria in UPEC-infected animals. Corresponding histological and morphological changes were found in epididymitis patients. The caput region was found to be unaffected in patients and the mouse model. LIMITATIONS, REASONS FOR CAUTION: Patient samples represented advanced cases of epididymitis that made surgical intervention necessary. WIDER IMPLICATIONS OF THE FINDINGS: Our data demonstrate the impact of epididymal segmentation, presumably a protective response mechanism against infectious invasion and bacterial ascent, during epididymitis and affirm the importance of rapid intervention. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants from the State of Hessen (LOEWE-MIBIE) and the DFG (KFO 181). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: No clinical trial involved.

Structure-based design and synthesis of potent matrix metalloproteinase inhibitors derived from a 6H-1,3,4-thiadiazine scaffold.

We describe a new generation of heterocyclic nonpeptide matrix metalloproteinase (MMP) inhibitors derived from a 6H-1,3,4-thiadiazine scaffold. A screening effort was utilized to identify some chiral 6-methyl-1,3,4-thiadiazines that are weak inhibitors of the catalytic domain of human neutrophil collagenase (cdMMP-8). Further optimization of the lead compounds revealed general design principles that involve the placement of a phenyl or thienyl group at position 5 of the thiadiazine ring, to improve unprimed side affinity; the incorporation of an amino group at position 2 of the thiadiazine ring as the chelating agent for the catalytic zinc; the placement of a N-sulfonamide-substituted amino acid residue at the amino group, to improve primed side affinity; and the attachment of diverse functional groups at position 4 or 5 of the phenyl or thienyl group at the unprimed side, to improve selectivity. The new compounds were assayed against eight different matrix metalloproteinases, MMP-1, cdMMP-2, cdMMP-8, MMP-9, cdMMP-12, cdMMP-13, cdMMP-14, and the ectodomain of MMP-14, respectively. A unique combination of the above-described modifications produced the selective inhibitor (2R)-N-[5-(4-bromophenyl)-6H-1,3,4-thiadiazin-2-yl]-2-[(phenylsulfonyl)amino]propanamide with high affinity for MMP-9 (K(i) = 40 nM). X-ray crystallographic data obtained for cdMMP-8 cocrystallized with N-allyl-5-(4-chlorophenyl)-6H-1,3,4-thiadiazin-2-amine hydrobromide gave detailed design information on binding interactions for thiadiazine-based MMP inhibitors.

Novel heterocyclic inhibitors of matrix metalloproteinases: three 6H-1,3,4-thiadiazines.

The title compounds, (2S)-N-[5-(4-chlorophenyl)-2,3-dihydro-6H-1,3,4-thiadiazin-2-ylidene]-2-[(phenylsulfonyl)amino]propanamide, C18H17ClN4O3S2, (I), (2R)-N-[5-(4-fluorophenyl)-6H-1,3,4-thiadiazin-2-yl]-2-[(phenylsulfonyl)amino]propanamide, C18H17FN4O3S2, (II), and (2S)-N-[5-(5-chloro-2-thienyl)-6H-1,3,4-thiadiazin-2-yl]-2-[(phenylsulfonyl)amino]propanamide, C16H15ClN4O3S3, (III), are potent inhibitors of matrix metalloproteinases. In all three compounds, the thiadiazine ring adopts a screw-boat conformation. The molecules of compound (I) show a short intramolecular N(Ala)-H...N(exo) hydrogen bond [N...N 2.661 (3) A] and are linked into a chain along the c axis by N(endo)-H...S(endo) and N(endo)-H...O(Ala) hydrogen bonds [N...S 3.236 (3) and N...O 3.375 (3) A] between neighbouring molecules. In compound (II), the molecules are connected antiparallel into a chain along the a axis by N(exo)-H...O(Ala) and N(Ala)-H...N(endo) hydrogen bonds [N...O 2.907 (6) and N...N 2.911 (6) A]. The molecules of compound (III) are dimerized antiparallel through N(exo)-H...N(endo) hydrogen bonds [N...N 2.956 (7) and 2.983 (7) A]. The different hydrogen-bonding patterns can be explained by an amido-imino tautomerism (prototropic shift) shown by different bond lengths within the 6H-1,3,4-thiadiazine moiety.

Fractures of the thoraco-lumbar spine with neurological deficits.

We present 78 patients with spinal cord injuries. Operation is not indicated in cord contusion, extended bleeding into the spinal canal or severe fracture dislocation. However, it would seem advisable to operate on patients with vertebral fractures, particularly at the lower thoracic and lumbar levels, if intraspinal bone fragments are detected by CT scan.

[Results of muscle biopsies in diphtheritic polyneuropathy. Light- and electron-microscopic examinations of muscle fibers, intramuscular nerves, motor endplates, and intramuscular vessels]. / Muskelbioptische Befunde bei der Diphtherie-Polyneuropathie. Licht- und elektronenmikroskopische Untersuchungen von Muskelfasern, intramuskulären Nerven, motorischen Endplatten udn intramuskulären Gefässen.

Muscle biopsies from the lower extremities of four patients with severe tetraplegic form of diphtheritic polyneuropathy were examined by modern techniques including histochemistry, electron microscopy and morphometric procedures. Until now comparable studies have not been published. The biopsies were removed during the acute stage of the polyneuropathy. We found scattered small angulated muscle fibers beside a more generalized slight atrophy predominantly of type 2 B fibers and targetoid-phenomenons or cores in type 1 fibers. Beside this neurogenic pattern there also were, corresponding with the results of electromyography, primary myogenic alterations with different degenerative phenomenons, suspicious of toxic origin as in cardiac muscle. The intramuscular vessels showed no abnormalities except some perivascular predominantly mononuclear cellular reactions with a remarkable number of cerebriform lymphoid cells, probably T-lymphocytes. No specific pathological alterations could be detected in 11 intramuscular nerves and two motor endplates. This may reflect the more proximal demyelination of human peripheral neurons by the diphtheria toxin as found in experimental diphtheria of the rabbit in contrast to the more distal type of the guinea pig.

[Neuromuscular manifestation of sarcoidosis (author's transl)]. / Neuromuskuläre manifestationen der Sarkoidose.

Three of our own observations of neuromuscular manifestation of sarcoidosis are presented. In two cases, a slowly progredient myopathic syndrome was evident. This syndrome developed in mid-life and showed asymmetrical distribution. In another case, a polyneuropathic syndrome was seen, which mainly affected motor function of the lower extremities. None of these patients had typical findings on chest x-rays. Histological proof of granulomatous alterations of skeletal muscle was the first indication of sarcoidosis. With reference to a further observation, the diagnostical value of muscle biopsy in sarcoidosis without neuromuscular manifestation is discussed.

[Clinical problems in extracranial vascular processes (author's transl)]. / Klinische Probleme bei extrakraniellen Gefässprozessen.

About 20 to 30% of the cerebral circulatory disturbances caused by arteriosclerosis depend on extracranial angiostenoses and vascular occlusions. Most frequently they are found in the region of the A. carotis interna, more seldomly the A. vertebralis or the A. subclavia and the aortic arch. The blood supply of the cerebral vascular regions concerned depends on the constitution and caliber of the collateral vessels, on their wall condition and elasticity, the blood pressure in the collateral circulation and the factor of time, the localization and the extension of the arterial disease. With regard to their effect asymptomatic stenoses and occlusions are differentiated from the transitory cerebral ischemia, the manifest encephalomalacia and the defective states. The clinical symptoms in extracranial angiostenoses and vascular occlusions, the necessary additional examinations to localize the process and to establish the differential diagnosis are discussed.